Changes in visual function and visual pathway in experimental glaucoma induced by intracameral injection of a chemically cross-linked hydrogel

Abstract

Purpose : We previously reported a new experimental glaucoma model induced by intracameral injection of an in situ cross-linked hydrogel, which provides chronic, mild to moderate elevation of IOP and leads to progressive retinal ganglion cell (RGC) degeneration.This study investigated the integrity of the visual pathways, retinal function, and behavioral response in the hydrogel-induced glaucoma model.

Methods : Hydrogel (hyaluronic acid-vinylsulfone and thiol groups) was injected intracamerally in C57BL/6 mice. Longitudinal diffusion tensor magnetic resonance imaging (DTI) was performed to characterize the degree of diffusion anisotropy in the optic nerve and the optic tract at 3, 7, and 28 days following hydrogel injection. Scotopic electroretinogram (ERG) response (a- and b-waves) and the positive scotopic threshold response (pSTR) were measured at baseline and 28 days. Optokinetic responses were measured at day 7, 14 and 28.

Results : Intracameral injection of hydrogel significantly increased the IOP from 8.9±0.1mmHg (mean±s.e.m.) to 18.2±0.5 mmHg over 4 weeks of follow-up (n=17, p<0.001), and led to progressive, regional loss of RGCs. Fractional anisotropy (FA) of the optic nerve and optic tract projected from the hypertensive eyes were smaller than those in the fellow eyes (n=6, p<0.001). The positive scotopic threshold response (pSTR), but not the scoptopic a- and b-wave, was significantly smaller in the hypertensive eyes (25.2±5.3µV) than the fellow eyes (37.6±2.5µV) (n=5, p=0.041). Visual acuity progressively declined in the hypertensive eyes (n=6, p<0.001).

Conclusions : Hydrogel-induced IOP elevation and retinal ganglion cell loss causes concomitant damage to the optic nerve and optic tract, and compromises inner retinal function. The new glaucoma model captures the key features of human glaucoma, which is pertinent to the investigation of neuroprotective and neuroregenerative therapies.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Fig 1. (A) Schematic of intracameral injection of cross-linked hydrogel and (B) corresponding longitudinal IOP profiles

 

Fig 2. Assessment of (A) optic nerve and optic tract integrity using DTI imaging, (B) behavioral response using optokinetic reflex, and (C) inner retinal function using ERG, over 4 weeks of IOP elevation